SUMMARY/ABSTRACT The placenta is both responsive and adaptive to maternal exposures, including many that affect stress/immune signaling. However, how it does this and the intricacies of normal developmental biology of the human placenta are still poorly understood. To tackle key questions in this area, we employ two unique tools: 1) cell sorting techniques that allow isolation of understudied placental cell types; and 2) deep-sequencing technologies that have hugely expanded the number of known short, non-coding RNAs in the human genome. We will apply these techniques to three unique cohorts with well-ascertained data and biological samples: 1) V- Norm: A normative, cross gestation, cohort from Vancouver, Canada; 2) V-SSRI: a cohort of women exposed to anti-depressants during their pregnancy; and 3) QF-2011: a cohort of women exposed to extreme weather (severe floods) in Queensland, Australia. Our research program encompasses three aims: Aim 1 is to provide a comprehensive placental atlas of cell-type, sex- and gestation-age specific epigenomic, transcriptomic, and metabolomic profiles through pregnancy and at term that will become an important clinical reference tool for assessing both normal and adverse pregnancy trajectories. Aim 2 is to better understand normal population variability amongst placentas from our three cohorts and evaluate their resilience to the effects of potential disruptors of stress signaling. To do this, we will use placental biomarkers of stress and inflammation to compare cohorts and compare these indicators to placental ?omics profiles. Aim 3 is to determine which placental biomarkers are reflected in samples of maternal blood in pregnancy and how this varies by gestational age. Although we now have the technological capabilities to generate large scale ?omics data sets, interpreting these in a useful manner requires the combined input of specialist placental biologists, genomics experts and strong knowledge of perinatal healthcare concerns. Our team has the qualified and experienced personnel to deal with these complex issues, along with the desire to coordinate with others in the placenta and ?omics communities towards a common agenda of improved maternal and newborn health. Through our work we will also strive to improve approaches to the design and analysis of placental ?omics studies.